Genetic wonders
to come: Some see boon, others calamity

If all goes as planned, scientists
within about a month will venture into a California strawberry patch the
size of a typical suburban lot and spray the young plants with about eight
trillion bacteria.

The bacterium, Pseudomonas syringae, is nothing out of the ordinary -
it is one of the thousands of microorganisms that live innocuously in the
soil, air and water of this planet, peacefully coexisting with humans and
other forms of life.

But in this instance, it represents a biotechnical revolution. With one
gene removed by scientists, it will be the first genetically engineered
organism to be released into the environment.

In its natural state, the microbe attracts ice crystals, causing frost
to form on plants. This version, however, is designed to inhibit freezing,
thus protecting the strawberries from an early, killing frost.

Agroeconomists believe that this strain of the bacterium - called
"ice minus" - could reduce the billions of dollars' worth of
crops lost each year to frost. Its commercial use could extend the growing
season in colder regions by up to two weeks.

And compared with other genetically altered organisms on the drawing
boards, ice-minus is a mere cave drawing.

For the coming decades, researchers are forecasting a host of
genetically designed wonders - plants that require little fertilizer
because they can draw their nitrogen from the air, microbes that consume
oil spills or detoxify hazardous waste, crops custom-designed to kill
insects and vaccines for dreaded diseases.

Even yesterday's announcement of the development of a nasal spray that
appears to help prevent the common cold came as a result of gene research:
Interferon, the once-rare antiviral substance used in the spray, can now
be mass-produced, thanks to gene-splicing.

A growing number of environmental groups, however, are seeking to
dampen the enthusiasm impelling the new technology. They are particularly
cautious about introducing new organisms into the environment, where they
could reproduce with unforeseen consequences.

For instance, some scientists believe that the same chemical structure
in the bacterium that causes ice crystals to form on plants also causes
ice crystals to form in the atmosphere, an essential step in the formation
of rain clouds. Should ice-minus reproduce and dominate its parent
bacteria in the environment, skeptics warn, it could reduce rainfall, or
worse, cause a drought.

"These are weird problems," said Jeremy Rifkin, president of
the Foundation for Economic Trends in Washington, which in November sued
the Environmental Protection Agency (EPA) to stop the strawberry-patch
experiment until it assesses the risks. He believes that the issues will
be magnified as researchers seek approval to release other new
microorganisms into the environment, with unpredictable results.

Research firms argue that too much regulation will hinder a growth
industry that is just a decade old, creating a competitive advantage for
Japanese and European researchers.

"There are some people who think if something is genetically
engineered, it's frightful," said Harvey S. Price, executive director
of the 48-member Industrial Biotechnology Association. He said the purpose
of the California experiment was to address the concerns that critics have
raised.

"Noboby's talking about killer tomatoes or the Andromeda
Strain," said Rifkin. "We're talking about more subtle things,
about the relationships of these things in the environment."

Skeptics believe that only a few of the genetically altered microbes
will cause environmental problems, but that the problems could be
calamitous.

"If history has taught us anything, it is that we have a litany of
problems with pesticides and leaks of toxins . . . and other things that
were introduced into the environment," said Jack Doyle, director of
the Agricultural Resources Project of the Environmental Policy Institute
in Washington.

"If we reflect on our recent technological problems, it should
give us pause."

*

The products of biotechnology are already being commercially produced,
locally and around the world, and some will soon be found in supermarkets
and hospitals.

Medical firms such as Centocor Inc. of Malvern have been producing such
products as human blood serum and monoclonal antibodies, the microscopic
"guided missiles" that can be designed to seek out specific
disease cells.

DNA Plant Technology Corp. in Cinnaminson this year will test-market
extra tasty carrots and celery it devised through a "tissue
culture" technique that is an accelerated form of traditional plant
breeding.

Charles Van Horn, the head of the biotechnology section of the U.S.
Patent Office, said his staff had tripled in the last two years, from 13
people to 38. Nevertheless, they are falling behind in reviewing patent
applications.

"You could say there has been a real increase of activity,"
he said. This year, according to rough industry estimates, $700 million
will be devoted to research and development of biotechnology, a slight
increase over last year.

Much of the technology involves the manipulation of DNA
(deoxyribonucleic acid), the chemical that is present in every living cell
and that makes up the genes that determine each characteristic of that
organism. DNA is the genetic blueprint.

By manipulating DNA, researchers can clone an organism many times over,
each time creating an exact duplicate. Medical firms such as Centocor, for
instance, have cloned antibodies that are now used for diagnosing and
treating specific disease cells. Centocor's cancer-testing kits, for
instance, are now sold abroad. The most difficult part of the process, the
company says, is identifying the antibodies, which occur naturally in
humans.

Likewise, researchers at DNA Plant Technology cross-breed plants by
mixing their cells in petri dishes, hoping that one cell will adopt the
desirable genetic characteristics of the other. When they achieve a
marketable combination - a particularly sweet carrot or celery without
stringy fibers - the scientists can reproduce the cells through cloning.

"It allows us to do what breeders have done for years, perhaps
more quickly and perhaps more selectively," said Dick Laster,
president of DNA Plant Technology.

Those techniques rely more on chance to achieve a desired genetic
combination than the gene-splicing involved with ice-minus, where a
researcher actually identified and removed a specific gene that was
controlling the bacterium's ice-formation properties. The technique is
also referred to as "recombinant DNA."

The discovery of the way in which ice crystals form on plants was made
by Steven E. Lindow, a plant pathologist at the University of California
at Berkeley. The crystals form around an enzyme secreted by Pseudomonas
syringae, which is present on most leaves. By removing the gene that
controlled the creation of the enzyme, Lindow found that plants coated
with ice-minus could survive in temperatures as low as 23 degrees
Fahrenheit. Untreated plants froze and died at 32 degrees.

Lindow sold the idea to Advanced Genetic Systems Inc. (AGS) of Oakland,
Calif. Two years ago, AGS applied to the federal government for a permit
to test ice-minus.

Rifkin's group at that time sued the government, contending that it had
no clear mechanism for handling biotechnology applications. As a result of
that lawsuit, the government put the ice-minus application on hold. A year
ago, the White House shifted responsibility for the applications from the
National Institutes of Health. Now, the EPA approves genetically
engineered pesticides, the Food and Drug Administration handles
gene-spliced drugs, and the Department of Agriculture reviews new plants.

In November, the EPA approved AGS's strawberry-patch experiment, which
the agency plans to monitor. "We decided the risk was sufficiently
low that they go ahead with the field tests," said William Schneider,
the EPA microbiologist who reviewed the ice-minus proposal. "We
conducted a reasonable, complete and thorough examination."

The EPA's Hazard Evaluation Division, in reviewing the application,
concluded that ice-minus would probably migrate outside the strawberry
patch and could survive indefinitely. However, the researchers contended
that because ice-minus is "genetically deficient," in that its
ice-making gene has been removed, it would not dominate its parent
bacterium in the environment.

Environmentalists, though, say U.S. history is replete with examples of
non-native creatures' proliferating disastrously after being introduced
into an environment for a specific purpose; gypsy moths, starlings and
kudzu vines are among those cited.

"You put a microbe out there," said Rifkin, "you can't
recall it and put it in a steel drum." His lawsuit is still pending
and could affect the planned ice-minus release.

Besides the possible reduction in rainfall, skeptics worry that
ice-minus could inadvertently prolong the growing seasons of many plants,
possibly disrupting a delicate natural balance in the food cycle.

*

The controversy developing over the ice-minus experiment only
foreshadows the clashes possible when more research firms try to introduce
more complicated organisms.

The only other application pending before the EPA for a gene-spliced
creation involves a proposal by the Monsanto Chemical Co. to incorporate a
naturally occurring insecticide into a soil bacterium, which would be used
to coat corn seed. The proposal is more advanced than ice-minus in that it
involves incorporating the insecticidal gene into the bacterium, rather
than merely removing a single gene from a microscopic organism.

The potential for such an insecticide would be immense: Theoretically,
the new organism would thrive in the soil along with the corn plant,
protecting its roots from black cutworms. With reduction of infestation,
production would increase.

Other research that reportedly is in the works would go one step
further than the Monsanto application by amalgamating the insecticide with
the plant itself, rather than within a soil bacterium. Scores of research
firms are trying to devise such insect-killing plants, including a team at
Temple University headed by biologist William R. Harvey.

"You remember the space program, when all those rockets were
blowing up on the launching pad?" said Harvey. "Well, the
science (of gene-splicing) is at that stage now."

Harvey's team is studying Bacillus thuringiensis, a naturally occurring
bacterial insecticide commonly known as BT. Most of the research into
genetically designed insecticides involve various forms of BT, some of
which affect specific insects. The Monsanto application involves a type of
BT that is believed to kill only black cutworms.

The Temple researchers are trying to identify the BT genes that produce
the insecticides in order to fuse those genes to plants. "All we're
doing is what nature is doing all the time," said Harvey. "We're
just doing it in a directed way."

Harvey's research budget is $227,000 this year, with the bulk of it
coming from the National Institutes of Health.

Howard T. Dulmage, a U.S. Department of Agriculture scientist in
Brownsville, Tex., who has isolated several BT strains, said he had doubts
that regulators would treat the insect-resistant plants as merely a slight
aberration from nature.

"I question whether this will be approved by the regulatory
agencies, because you're introducing a toxin into a plant," he said.
"I don't think anybody knows what the long-term effect of that will
be."

Officials of Rohm & Haas Co., which is contributing $30,000 to
Harvey's effort, announced earlier this year that a European research team
it is sponsoring had spliced BT genes to the cells of a plant. But they
declined to disclose whether the plant effectively killed insects, noting
that their competitors were involved in similar research.

"Because of the competition and the dollars at stake, these
companies are playing this so close to the vest that we only learn of
their plans when they apply for a permit," said Doyle of the
Environmental Policy Institute.

The EPA's Schneider acknowledged that the new microorganisms would
present a difficult challenge to regulators, but not an insurmountable
one. "You know an organism will kill one target species, but you're
not sure what else it will affect," he said. "So you test it
against a representative cross section of other species. It's the same
with chemicals."

But Doyle argues that the microorganisms are living creatures, not
toxic chemicals. "The microbial realm is different from
petrochemicals," he said. "We're in uncharted territory there.
We don't know a hell of a lot about unaltered organisms and why they
occupy a particular niche in the ecosystem.

"We're on a breakthrough of a really fundamental knowledge in the
plant sciences. Some of these applications may be very productive and have
the net beneficial effect in the long run of reducing our reliance on
pesticides."

The naysayers acknowledge that the technology, powered by a potent
commercial and political momentum, will prevail over their calls for
caution. Said Rifkin: "It's part of our cultural tradition - 'If it
can be done, do it. Let's worry about the consequences later.'

"There may be a lot of benefits to this technology, but there's a
lot of costs. . . . If we don't discuss these questions at the beginning
of the technological revolution, then the middle of the process will be
too late and by the end of the process, it won't matter."